Klinefelter's syndrome and bone mineral density: is osteoporosis a constant feature?

Data on bone mineral density (BMD) in Klinefelter syndrome (KS) are scarce and contradictory. The aim of the present study was to investigate BMD in patients with KS and in healthy controls with special attention to gonadal status.

We investigated 26 patients with KS (30±9 yr) who had never been treated with testosterone. Thirty-nine age-matched healthy males served as controls. We assessed BMD by performing dual energy X-ray absorptiometry and measured serum hormone levels, including total testosterone (T), free testosterone, estradiol (E2), leptin. The estrogen to androgen ratio (E2/T) was used as an indirect measure for aromatase activity.

No difference was found in BMD at femoral neck (1.06 ± 0.16 vs 1.04 ± 0.14 g/cm²), or at lumbar spine (1.00 ± 0.09 vs 1.03 ± 0.11) between patients and controls. Two patients and one control were classified as osteoporotic (T-score ≤ -2.5). Compared with controls, patients had lower levels of T and free testosterone, similar E2 levels, and increased E2/T (P < 0.05). In KS patients, leptin was significantly higher and correlated positively with E2/T (r = 0.484, P = 0.02). E2/T correlated with femoral neck BMD (r = 0.566, p = 0.02), T and free T correlated with lumbar spine BMD (r = 0.433, P = 0.05 and r = 0.534, P = 0.05).

Osteoporosis is not a constant feature in young patients with KS, even without testosterone substitution. The aromatisation of T into E2, related to adiposity, may contribute to the achievement and maintenance of normal BMD in some KS patients.